The causes of breast cancer have not been clearly established, but various factors such as female hormones, family history, past medical history, birth history and dietary habits have been considered. According to a survey of the National Statistical Office in 2005, the incidence of breast cancer has been rapidly increasing in these years and overtook the incidence of cervical cancer in 1998. Consequently, while comprising 16.1% of Korean female cancer patients occurred in 2001, the breast cancer surpassed a gastric cancer to hold the first rank. In particular, in 2002, the breast cancer (11.1%) was ranked as a most rapidly increasing cancer in comparison with 2001. In women undergoing physiologically vigorous changes such as a low birth rate, a short feeding period, a early menarche and a late menopause, the incidence of female hormone stimulation has been rapidly increased, thereby increasing a sensitivity of mammary tissue, westernizing the eating habits and polluting a living environment. For these reasons, the incidence of breast cancer is dramatically increased in the recent years.
In view of the actual situation of the current westernization, it is anticipated that increasing the incidence of breast cancer and the mortality due to breast cancer will be kept for a fairly long time in the future. Breast cancer usually results in symptoms such as a lymph node metastasis or an invasion of surrounding tissue due to the growth of cancer cells. However, the majority of the breast cancer can be checked by self-diagnosis without any symptoms. Therefore, in order to reduce the mortality due to breast cancer, it is very important to effectively make an early diagnose of breast cancer (Tuli et al., Breast J., 12: 343-348, 2006).
To diagnose breast cancer, a number of methods have been complexly used. Until now, 70% of breast cancer patients have been hospitalized by the self-diagnosis. However, this self-diagnosis has a disadvantage that it is very difficult to distinguish between malignant tumor and benign tumor lump. In addition, the method for diagnosing breast cancer comprises mammography, ultrasonography, fine-needle aspiration cytology, magnetic resonance radiography and the like, but it is important to check the cancer through biopsy eventually. The mammography refers to a method of taking a breast with X-ray and identifying a breast cancer, and it is excellent in distinguishing whether a tumor lump is benign or malignant. Also, the mammography is a method of finding a latent tumor lump and it is most effective in diagnosing an initial cancer before touching the lump by self-diagnosis. However, the mammography has a disadvantage that a diagnostic yield is decreased in Korean women whose milk line is well-developed like a young women or whose breast is small and fibrous. Further, it is controversy that frequently taking the breast with X-ray may lead to a breast cancer. As an alternative to such mammography, the ultrasonography is used. The ultrasonography is effective in differentiating between a cyst and a hard lump, but the ability to differentiate between malignant tumor and benign tumor lump is decreased.
In order to supplement the disadvantages encountered with such conventional diagnosis methods, there was an attempt to diagnose a breast cancer by measuring a concentration of tumor marker in a blood of patient (Clinton et al., Biomed Sci. Instrum. 39: 408-414, 2003; Rui et al., Proteomics. 3: 433-439, 2003; Soletormos et al., 48: 229-255, 2001). However, the importance of the diagnostic or prognostic factor of these tumor markers is studied, but its use has still been limited, there being no breast cancer marker officially recommended in the art.
Given the above circumstances, the present inventors have conducted a number of extensive researches in order to develop a method for using, in the diagnosis of breast cancer, a protein marker wherein the protein amount is specifically changed in blood from a breast cancer patient. As a result, the inventors have discovered that comparing the change patterns according to breast cancer of the marker set consisting of a plurality of biomarkers can more effectively diagnose the breast cancer than the method by the change of a single biomarker. In order to effectively track the plurality of protein markers, the inventors have discovered that the breast cancer can be conveniently diagnosed by monitoring the expression level of peptide capable of representing each biomarker protein through a multiple reaction monitoring. The present invention has been completed on the above discovery.